Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report

Abstract Background Polygenic mutations play a significant role in the etiology of various growth-related disorders and bone deformities, influencing multiple physiological processes. Understanding the impact of polygenic mutations is crucial for the diagnosis, genetic counseling, and management of...

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Main Authors: Hui Wang, Jinhui Wang, Darong Chen
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Italian Journal of Pediatrics
Subjects:
Online Access:https://doi.org/10.1186/s13052-025-02054-z
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author Hui Wang
Jinhui Wang
Darong Chen
author_facet Hui Wang
Jinhui Wang
Darong Chen
author_sort Hui Wang
collection DOAJ
description Abstract Background Polygenic mutations play a significant role in the etiology of various growth-related disorders and bone deformities, influencing multiple physiological processes. Understanding the impact of polygenic mutations is crucial for the diagnosis, genetic counseling, and management of these complex conditions. Case presentation A boy first evaluated at 9 years and 10 months for short stature was diagnosed with compound heterozygous mutations in PLEC, CD96, and RNU4ATAC genes, with comorbid congenital multiple epiphyseal dysplasia and growth hormone deficiency. These mutations collectively contributed to severe short stature, skeletal deformities, and delayed neurodevelopment. Orthopedic surgeries were performed at 9 years and 10 months (first intervention), 11 years and 6 months (second intervention), and 12 years and 9 months (third intervention), while growth hormone therapy (GHT) was initiated at 11 years and 10 months. Over 25 months of GHT, his height increased by 18 cm, bone age advanced by five years, and gait improved. Final clinical evaluation at 13 years and 11 months confirmed sustained improvements in height (137 cm) and motor function. Conclusion This case involves a child with short stature caused by rare mutations of PLEC, CD96, and RNU4ATAC. This is the first case report documenting the concurrent presence of all three rare mutations. Orthopedic surgery and GHT were employed to improve the patient’s development and quality of life. We propose that early identification of high-risk factors, genetic screening, and comprehensive treatment can enhance therapeutic effectiveness and improve the patient’s quality of life.
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spelling doaj-art-d53d312989f9464d8efa896ff1f2e7cf2025-08-20T04:02:55ZengBMCItalian Journal of Pediatrics1824-72882025-07-015111710.1186/s13052-025-02054-zConcurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case reportHui Wang0Jinhui Wang1Darong Chen2Department of Children Healthcare, School of Medicine, Xiang’an Hospital of Xiamen University, Xiamen UniversityDepartment of Clinical Laboratory, Children’s Hospital of Fudan University at Xiamen, Xiamen Children‘s HospitalEmergency Department, Xiamen Fifth HospitalAbstract Background Polygenic mutations play a significant role in the etiology of various growth-related disorders and bone deformities, influencing multiple physiological processes. Understanding the impact of polygenic mutations is crucial for the diagnosis, genetic counseling, and management of these complex conditions. Case presentation A boy first evaluated at 9 years and 10 months for short stature was diagnosed with compound heterozygous mutations in PLEC, CD96, and RNU4ATAC genes, with comorbid congenital multiple epiphyseal dysplasia and growth hormone deficiency. These mutations collectively contributed to severe short stature, skeletal deformities, and delayed neurodevelopment. Orthopedic surgeries were performed at 9 years and 10 months (first intervention), 11 years and 6 months (second intervention), and 12 years and 9 months (third intervention), while growth hormone therapy (GHT) was initiated at 11 years and 10 months. Over 25 months of GHT, his height increased by 18 cm, bone age advanced by five years, and gait improved. Final clinical evaluation at 13 years and 11 months confirmed sustained improvements in height (137 cm) and motor function. Conclusion This case involves a child with short stature caused by rare mutations of PLEC, CD96, and RNU4ATAC. This is the first case report documenting the concurrent presence of all three rare mutations. Orthopedic surgery and GHT were employed to improve the patient’s development and quality of life. We propose that early identification of high-risk factors, genetic screening, and comprehensive treatment can enhance therapeutic effectiveness and improve the patient’s quality of life.https://doi.org/10.1186/s13052-025-02054-zShort statureBone deformitiesPolygenic mutationsCase reportGrowth hormone deficiency
spellingShingle Hui Wang
Jinhui Wang
Darong Chen
Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
Italian Journal of Pediatrics
Short stature
Bone deformities
Polygenic mutations
Case report
Growth hormone deficiency
title Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
title_full Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
title_fullStr Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
title_full_unstemmed Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
title_short Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report
title_sort concurrent mutations in rnu4atac plec and cd96 in a child with severe short stature and skeletal dysplasia a case report
topic Short stature
Bone deformities
Polygenic mutations
Case report
Growth hormone deficiency
url https://doi.org/10.1186/s13052-025-02054-z
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